Project Summary This proposal builds upon the advances from the SBIR-Phase I program (R43GM123887), targeting the development of recombinant human MG53 (rhMG53), a novel tissue repair protein, as a topical therapeutic agent to facilitate healing of chronic wounds. Wound care represents a challenging problem to the public health, as no effective treatments for chronic non-healing wounds are available. MG53 is an essential component of cell membrane repair that protects against tissue injuries. Research and development efforts at TRIM-edicine, Inc. have established that rhMG53 protein has great potential in facilitation of wound healing and reduction of scar formation. From the SBIR-Phase I program we obtained proof-of-concept data that support our translational and commercialization effort toward developing rhMG53 as a protein therapeutic to treat chronic wounds. We developed the protocol for scale-up production of rhMG53 and the analytical methods for quantification and quality control of rhMG53. We obtained promising data to support the efficacy for rhMG53 in treatment of cutaneous wounds in multiple animal models. We also conducted non-GLP toxicological studies in rodent and dog models and found that rhMG53 as a topical cream did not cause irritation to the skin. No-observed-adverse-effect-level with intravenous administration is >40 mg/kg in rats, supporting the safety of rhMG53 to treat chronic wounds. In this SBIR-Phase II application, we outlined a milestone-driven research plan with deliverable matrixes to reach the goal of filling an Investigational New Drug (IND) application with the FDA to initiate the human clinical trials. Our understanding of MG53?s biological role in tissue repair-regeneration support the multi-cellular function of MG53 in promoting the healing process, as well as in mitigation of scarring associated with dermal injuries. We envision that rhMG53 has advantage over the current paradigms to treat human chronic wounds.